tbuckley/cabot-search huggingface dataset:
PB2296: THE PROGNOSTIC ROLE OF NEUTROPHIL TO LYMPHOCYTE RATIO AND PLATELET TO LYMPHOCYTE RATIO IN COVID-19 PATIENTS: A MONOCENTRIC STUDY
Authors: W. Boufrikha, R. Mezriqui, N. Slama, S. Chouchene, S. Abidi, Z. Mlayah, A. Benabdeljelil, M. Ftita
Journal: HemaSphere (2022)

Background: Several studies described numerous factors to affect the prognosis and predict the severity of COVID-19. Inflammatory markers like neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been used to prognosticate cancers and inflammatory diseases such as COVID-19. Aims: To describe and identify the predictive factors of intensive care unit admission in COVID-19. Methods: This is a retrospective study conducted in Fattouma Bourguiba University Hospital of Monastir, Tunisia, from April 2020 to February 2022. Our study concerned patients diagnosed with COVID-19 during this period. NLR and PLR were investigated for each patient at the first day of hospitalization and all patients were followed in order to notice who required intensive care unit (ICU). Results: We enrolled 569 patients. The median age was 62 years old (ranged 1-96) and we had male predominance (sex ratio 1.63). Seventy one per cent of our population had lymphopenia and polynucleosis was found in 45.7% of cases. The median NLR and the median PLR were respectively 6.37 and 232.05. NLR >3, NLR >9 and PLR >180 accounted for 77%, 35% and 57.9% respectively. Twenty three per cent of our population required hospitalization in ICU and this condition was significantly associated with elevated NLR and elevated PLR in univariate analysis (Table 1). Table 1: - Univariate analysis Total ICU N % N % p NLR >3 431 77 112 26 0.002 NLR>9 196 35 73 37.2 0.000 PLR >180 324 57.9 92 28.4 0.000 Age >60 years 310 54.5 76 24.5 0.250 Age >75 years 81 14.2 12 14.8 0.068 In multivariate analysis, elevated NLR (>9) (hazard risk [HR] 2.83, 95% confidence interval [CI] 1.75–4.57) was retained as only factor associated with intensive care hospitalization. Summary/Conclusion: Many factors can modify the clinical outcome in COVID-19 patients. Our study supports the fact that elevated NLR (>9) may be a prognostic biomarker.
PB1911: A COMPREHENSIVE EHEALTH IMPLEMENTTION GUIDE CONSTRUCTED ON A QUALITATIVE CASE STUDY ON BARRIERS AND FACILITATORS OF THE DIGITAL CARE PLATFORM CMYLIFE, FOR PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: L. Verweij, Y. Smit, N. Blijlevens, R. Hermens
Journal: HemaSphere (2022)

Background: Substantial proliferation of eHealth has enabled a move in patient-centred cancer care from the traditional in-person care model to real-time, dynamic, and technology supported on-demand care. However, in general, the uptake of these innovations is low. Studies show that eHealth is helpful in providing patient empowerment through e.g. providing high quality and timely information, enabling self-monitoring and shared decision making, but dropout rates are high and guidance for optimal implementation is lacking. Aims: To explore barriers to and facilitators for nationwide implementation and consolidation of CMyLife, a multi-component, patient-centred, digital care platform for patients with chronic myeloid leukemia, and to construct a comprehensive implementation guide for digital care platforms in general. Methods: The first qualitative case study of a digital care platform like CMyLife was performed including five focus group- and eighteen in-depth interviews with stakeholders. Data were collected using a semi-structured interview guide, based on the frameworks of Grol and Flottorp. Transcripts of the interviews were analysed and barriers and facilitators were identified and categorized according to the frameworks. An iterative process including participation of the main stakeholders and using the CFIR-ERIC framework led to creating a comprehensive implementation guide for digital care platforms in general. Results: In total, 45 barriers and 41 facilitators were identified. Main barriers were lack of connectivity between information technology systems, changing role for both health care providers and patients, insufficient time and resources, doubts about privacy and security of data, and insufficient digital skills of users. Main facilitators mentioned were motivating patients and health care providers by clarifying the added value of use of a digital care platform, clear business case with vision, demonstrating (cost) effectiveness, using an implementation guide, and educating patients and health care providers about how to use CMyLife. Based on these barriers and facilitators a clear and comprehensive implementation guide was developed for digital care platforms in general. Summary/Conclusion: Several barriers to and facilitators for implementation were identified, a clear overview was presented, and a unique comprehensive implementation guide was developed for lancing future digital care platforms in daily clinical practice. The next step is to validate the implementation guide in other (oncological) diseases.
PB2048: EFFICACY AND SAFETY OF RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS: A RETROSPECTIVE MULTICENTER STUDY
Authors: C. Chen, S. Ma, F. Yan, H. Zhao, X. Chu, H. Zhang, X. Deng, Z. Liu, D. Li, T. xiao, C. Yuan, Z. Wang, G. Liu, M. Hou, Y. Yu
Journal: HemaSphere (2022)

Background: Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor currently used in the treatment of Myelofibrosis (MF). Ruxolitinib confirmed improvements in splenomegaly, MF-related symptoms and survival benefit in COMFORT and JUMP studies. At present, the real-world data on the efficacy and safety of ruxolitinib in the treatment of MF in China is still insufficient. Aims: The aim of this study was to evaluate the efficacy and safety of ruxolitinib in patients with MF and to provide guidance for the usage of ruxolitinib in MF in China. Methods: This was a retrospective, multicenter study of MF patients who received ruxolitinib treatment in Shandong province from August 2012 to December 2021. Data were analyzed using SPSS. Overall survival (OS) and Event-free survival (EFS) were estimated using the Kaplan– Meier method. Results: A total of 130 MF patients were recruited, among which 97 (74.6%) primary MF patients and 33 (25.4) secondary MF patients were involved. Most patients started at dose of 20 mg bid (n=44, 33.1%), while other patients started ruxolitinib treatment at lower doses, including 15 mg bid (n=29, 21.8%), 5 mg bid (n=26, 19.5%) and 10 mg bid (n=23, 17.3%). The most common adverse events (AEs) were anemia (23.1%), thrombocytopenia (15.4%), lung infection (9.2%) and elevated aminotransferase (5.4%). Overall, Ruxolitinib led to remarkable reductions in spleen length and MF-related symptoms in most patients. 74.7% (71/95) of patients experienced an improvement in splenomegaly at any time after medication with a median reduction of 33.3% (Fig. A). At week 24, 73.8% (45/61) of the evaluated patients had a ≥25% decrease in spleen length, therein 45.9% (28/61) reached a ≥50% decrease (Fig. B). 87.5% (70/80) of patients experienced decreased MPN-SAF TSS with a median of -63.4% (Fig. C). The median reduction of more than 50% from baseline in all MF symptoms was observed in 53 assessed patients (Fig. D). The estimated OS probability of Low/ Int-1 patients was 96.7% at 24 months. The estimated OS probability of Int-2/ High patients was 83.9% at 24 months (Fig. E). Primary causes of death on study included MF (n=7), lung infection (n=1), cerebrovascular accident (n=1) and AML (n=1). The median EFS of Low/ Int-1 patients was 21 months, while the median EFS of Int-2/ High patients was 8 months (Fig. F). Image:Summary/Conclusion: In summary, Chinese MF patients receiving ruxolitinib showed improved splenomegaly and MF-related symptoms. Besides no new safety concerns were found. Less adverse events were observed in lower risk of MF patients during ruxolitinib treatment. Generally, the efficacy and safety profiles of ruxolitinib in the treatment of Chinese MF patients were basicly consistent with other studies.
P1504: AN AUDIT OF PAIN EDUCATION IN PATIENTS WITH SICKLE CELL DISEASE
Authors: Y. Zhou, R. Auturally, V. Garcia, R. Jolley, M. Besser
Journal: HemaSphere (2022)

Background: Pain crises represent the primary reason for hospital care-seeking in individuals with sickle cell disease (SCD). The NICE guideline CG143 emphasises that patient should be treated as experts in the pain management of their sickle cell disease. Aims: To assess the performance of acute sickle cell pain crisis management at Cambridge University Hospital (CUH) and assess methods of secondary prevention of admission for pain crisis through patient pain education. Methods: Patient admission records during the year of 2021 were reviewed for a population of 85 SCD patients registered at Cambridge University Hospital (CUH). For these encounters, patient assessment at presentation, primary analgesia and ongoing management were audited against CG143 standards. All SCD patients registered with CUH were contacted for a telephone interview to discuss home pain management. Results: In a population of 85 patients living with SCD, there were 22 admissions in 17 patients during 2021, of which 5 patients had multiple admissions. Auditing CUH performance against the NICE CG143 guidelines, it was found that initial pain relief was provided within 30 minutes of presentation in 15 out of the 21 relevant admissions (71%). However, none of the patients had documented discussion of pain control education, any psychological support they may need nor were encouraged to use their own coping mechanisms for dealing with acute pain in their hospital notes. Following on from this, we conducted telephone interviews and received a total of 51 responses of which 13 patients were admitted to hospital with sickle cell pain in 2021. In the 46 patients who experience sickle cell pain crises, 20 had strong opiates, 27 had weak opiates, and all 46 had a supply of paracetamol/non-steroidal anti-inflammatory drugs (NSAIDs). 8/20 (40%) patients with a home supply of strong opiates were admitted to CUH with an acute sickle cell pain crisis in 2021 compared to 5/26(19.2%) in those who did not have strong opiates at home. Notably, only 6/46 patients were familiar with the World Health Organisation pain ladder. 2 of 6 patients who were aware of the WHO pain ladder had an admission to CUH in 2021, while 11 of 40 patients who were not aware had an admission to CUH in 2021. The findings are summarised in Table 1. Image:Summary/Conclusion: Our audit has demonstrated a significant gap in the management of acute sickle cell pain crises at CUH with the absence of patient pain education. This may have contributed to the number of admissions of SCD patients to CUH. The limited patient knowledge of optimal use of pain control in line with WHO pain ladder is significant, given that most episodes are managed at home. Frequent painful crises are associated with psychological issues and poor engagement in normal daily activities. Better home pain control should be a future priority for our service.
P835: GENETIC BACKGROUND AND CLINICAL CHARACTERISTICS OF CONGENITAL NEUTROPENIAS IN ISRAEL
Authors: O. Steinberg-Shemer, L. Yeshareem, S. Noy-Lotan, O. Dgany, T. Krasnov, G. Berger Pinto, B. Bielorai, A. A. Kuperman, R. Laor, N. Mandel-Shorer, A. Ben Barak, C. Levin, A. Mahdi, H. Miskin, S. Revel-Vilk, D. Levin, M. Benish, T. Zuckerman, O. Wolach, I. Pazgal, O. Gilad, T. Goldberg, J. Yacobovich, S. Izraeli, H. Tamary
Journal: HemaSphere (2022)

Background: Congenital neutropenias comprise a heterogenous group of disorders causing low neutrophil counts with a variable clinical presentation. Patients may suffer from severe infections and have a high risk of myeloid transformation. To date, over 30 genes are known to cause congenital neutropenias, with a diverse relative frequency in different ethnicities. Understanding the spectrum of genetic causes of neutropenia in ethnically diverse populations and the related clinical presentation may direct the molecular work-up and clinical care. Israel is enriched with multiple ethnicities and high consanguinity. Aims: To evaluate the clinical and genetic spectrum of patients with congenital neutropenias in Israel. Methods: All patients diagnosed with congenital neutropenia from the Israeli Inherited Bone Marrow Failure registry were included. Data were extracted from the registry and patients’ charts. Sanger sequencing was first performed for ELANE or G6PC3, followed by less commonly mutated genes. In recent years, patients with wild-type ELANE/G6PC3 were referred for targeted next generation sequencing, followed by whole exome sequencing. Results: The cohort encompasses 66 patients, from 50 families, including 7 with cyclic neutropenia. Fifty patients (76%) were genetically diagnosed; 22 (33% of the cohort) had mutations in ELANE, 9 (13.6%) had homozygous G6PC3 mutations, 7 (10.6%) SBDS mutations, 6 (9%) patients had SRP54 mutations, two each had heterozygous GFI1 and homozygous JAGN1 mutations and one each had TAZ and SLC37A1 mutations. All patients with G6PC3 and GFI1 mutations were of consanguineous Muslim Arab origin. Extra-hematopoietic manifestations were common among patients with mutations in G6PC3. Most patients (82%) presented with severe infections and this was also the most common cause of death. Eight patients (12%) developed myeloid transformation; in 6 of those a somatic molecular work-up was performed, and truncating mutations in the granulocyte-colony stimulating factor were detected in 4. Eighteen (27%) patients underwent hematopoietic stem cell transplantation, most often due to insufficient response to treatment with granulocyte-colony stimulating factor. Summary/Conclusion: The prevalence of genes causing congenital neutropenias in Israel is unique, as it includes a relatively high frequency of patients with mutations in G6PC3 and an absence of patients with HAX1 mutations, thus directing the genetic work-up and the clinical care. Similar to other registries, a molecular diagnosis was not achieved for 24% of the patients, suggesting yet unknown genetic causes.
P1399: EXTRAMEDULLARY HEMATOPOIESIS IN THE ADULT ADRENAL GLAND AS A MODEL OF THE MINIMAL HEMATOPOIETIC NICHE
Authors: A. Alonso Calleja, F. Schyrr, S. F. Lopes, S. Gebhard, R. Sarkis, A. Oggier, O. Naveiras
Journal: HemaSphere (2022)

Background: Hematopoietic Stem and Progenitor Cells (HSPCs) reside in the hematopoietic niche, a structure that regulates the balance of cellular quiescence, self-renewal and commitment towards progenitor cells in a demand-adapted manner. The bone marrow (BM) hematopoietic niche is formed by several cellular players, mainly endothelial cells, osteoblasts, adipocytes, and a variety of stromal cells. While the BM niche contains a complex stromal population, evidence exists for simpler, albeit functional, extramedullary hematopoietic (EMH) niches. EMH can be found associated to adipose tissue. An example of adipose-associated EMH is myelolipoma, an adrenal tumor composed of myeloid and adipose tissue. Myelolipoma is frequent in patients with congenital adrenal hyperplasia, an endocrine disorder that associates an increase in ACTH. Aims: We aimed to produce an EMH animal model that would recapitulate myelolipoma to study a minimalistic, boneless hematopoietic niche. Methods: We designed a strategy to induce EMH in the adrenal gland. For this, we injected hematopoietic cytokines (Granulocyte colony-stimulating factor (G-CSF)) and pituitary axis hormones (ACTH) as well as androgens (testosterone) in splenectomized C57BL/6J mice and studied the hematopoietic-supportive capacity of the induced adrenal glands. Results: Here, we show that the adult adrenal gland can be transformed into a hematopoietic supportive environment. Upon hormonal stimulation, the adult adrenal gland can be induced to recruit and host hematopoietic cells, including serially transplantable HSCPs. The adrenal stroma supports HSPC proliferation and function; furthermore, the adrenal stroma contains a CXCL12+ population, reminiscent of BM CXCL12-Abundant Reticular (CAR). These findings are mirrored by the presence of CXCL12+ cells in human myelolipoma samples, a benign adrenal tumor composed of adipose and hematopoietic tissue. Summary/Conclusion: We present our model as a novel tool to increase our understanding of the physiology of hematopoietic support and to facilitate the development of a boneless niche model.
Author Correction: Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome
Authors: Brian J. Golbourn, Matthew E. Halbert, Katharine Halligan, Srinidhi Varadharajan, Brian Krug, Nneka E. Mbah, Nisha Kabir, Ann-Catherine J. Stanton, Abigail L. Locke, Stephanie M. Casillo, Yanhua Zhao, Lauren M. Sanders, Allison Cheney, Steven J. Mullett, Apeng Chen, Michelle Wassell, Anthony Andren, Jennifer Perez, Esther P. Jane, Daniel R. David Premkumar, Robert F. Koncar, Shideh Mirhadi, Lauren H. McCarl, Yue-Fang Chang, Yijen L. Wu, Taylor A. Gatesman, Andrea F. Cruz, Michal Zapotocky, Baoli Hu, Gary Kohanbash, Xiuxing Wang, Alenoush Vartanian, Michael F. Moran, Frank Lieberman, Nduka M. Amankulor, Stacy G. Wendell, Olena M. Vaske, Ashok Panigrahy, James Felker, Kelsey C. Bertrand, Claudia L. Kleinman, Jeremy N. Rich, Robert M. Friedlander, Alberto Broniscer, Costas Lyssiotis, Nada Jabado, Ian F. Pollack, Stephen C. Mack, Sameer Agnihotri
Journal: Nature Cancer (2022)
PB1804: CLINICAL AND DEMOGRAFIC RELATIONS OF BAALC GENE OVEREXPRESSION IN AML PATIENTS - A SINGLE-CENTER OBSERVATIONS
Authors: E. Aleksov, M. Jagurinoski, I. Tonev, K. Venkov, M. Genova, G. Balatzenko, Y. Lazarova, G. Arnaudov, B. Spasov
Journal: HemaSphere (2022)

Background: Impaired regulation of the gene expression of BAALC (brain and acute leukemia, cytoplasmic) gene, which plays a role in the regulation of myeloid differentiation, leads to changes in functional gene activity and probably acts as a component of the leukemogenesis in acute myeloid leukemia (AML). Aims: To analyze the frequency and clinical significance of overexpression of the BAALC gene in patients with AML. Methods:: A total of 67 samples of patients (33% men and 34 % women) with an overt AML with >20% blast cells, excluding acute promyelocytic leukemia, were included in this study. The diagnosis was made according to the criteria of WHO classification (2016). BAALC gene expression was assessed by polymerase chain reaction after reverse transcription (RT-PCR). Risk stratification was done according to ЕLN. Results: The overexpression of the BAALC gene was found in 33/67 (49.3%) AML patients of whom 14/33 (42.4%) male and 19/33 (55.9%) female with median age 56.4 years (range, 23-77 years). BAALC -positive cases were distributed as follows: AML - not otherwise specified (AML NOS) 11/33 (33.3%); AML with MDS-related changes 10/33 (30 %); AML with recurrent genetic abnormalities 6/33 (18.1%) and therapy related AML 6/33 (18.1%). In the analysis of the main hematology and clinical parameters, we observed a tendency for higher BAALC overexpression in the following groups of AML patients: • AML patients with WBC ≤10.5x10^9/l 11/19 (57.8%), vs patients with WBC ≥10.5x10^9/l 14/33 (42.4%) • AML patients with neutropenia <2.1x10^9/l 19/33 (57.6%), vs patients with neutrophilia >6.4x10^9/l 8/20 (40%). • AML patients with thrombocytopenia <50G/l 17/29 (58.6%), vs patients with platelets count >50G/l 10/28 (35.7%); • AML with MDS-related changes/therapy related AML 17/26 (65.4%), vs other types 16/41 (39%) • AML in the groups with an unfavorable karyotype 12/16 (75%) vs 18/39 (46.1%) with good/intermediate. • AML patients who failed to achieve remission 24/34 (70.5%) vs patients who achieved remission - 9/26 (34.6%). The mean overall survival (OS) was poorer in BAALC (+) compared to BAALC (-) patients (respectively 11.7 months vs. 18.6 months, (p = 0.62). Summary/Conclusion: Our single-center observations confirmed previous publications that BAALC gene overexpression is a frequent genetic abnormality in AML patients. There is a tendency for a correlation between the BAALC overexpression and some unfavorable prognostic indicators, as well as a trend to shorter OS. Our data show that future studies of the clinical significance and prognostic role of BAALC gene would be worth.
Engineered Delivery of Dental Stem‐Cell‐Derived Extracellular Vesicles for Periodontal Tissue Regeneration (Adv. Healthcare Mater. 12/2022)
Authors: Jana Zarubova, Mohammad Mahdi Hasani‐Sadrabadi, Erfan Dashtimoghadam, Xuexiang Zhang, Sahar Ansari, Song Li, Alireza Moshaverinia
Journal: Advanced Healthcare Materials (2022)

Periodontal Tissue Healing Article number 2102593 by Alireza Moshaverinia and co-workers focuses on the development of microparticles that enable the microenvironment-sensitive release of extracellular vesicles (EVs) by metalloproteinases. Upon their release, EVs derived from gingival mesenchymal stem cells modulate immune cells to promote regeneration of the damaged periodontal tissue. The increased retention of immunomodulatory EVs by microparticles at the affected tissue shows better pro-regenerative effects than free EVs.